Using a dual-isohypercapnic technique, the authors determined the effect of equipotent doses of methohexital (1.5 mg/kg) and etomidate (0.3 mg/kg) on the ventilatory response to CO2(VERCO2) in six healthy volunteers. Speed of induction and duration of hypnosis did not differ significantly between the two drugs. Within 2 min after injection, the slope of VERCO2decreased significantly after both methohexital (from 2.52 to a minimum of 0·15 1.min−1mmHg−1,P< 0.05) and etomidate (from 2.56 to a minimum of 0.62 1·min−1·mmHg−1,P< 0.05); the magnitude of this depression did not differ significantly between the drugs. Methohexital also caused a significant decrease in minute ventilation at end-tidal PCO2of 46 mmHg (VE46) from 14.6 to 4.3 1·min−1within 60 s after injection (P< 0.05). In contrast, after etomidate VE46 gradually increased from 17.9 1·min−1to a maximum of 31.6 1 ± min−1at 3.5 min after injection (P< 0.05); respiratory rate increased significantly, while changes in tidal volume were not significant. Effects of etomidate and methohexital on VE46 differed significantly (P< 0.001). These data indicate that, while etomidate and methohexital similarly depress the medullary centers that modify ventilatory drive in response to changing CO2tensions, ventilation at any given CO2tension is greater after etomidate than after methohexital. This indicates that etomidate may cause a CO2-independent stimulation of ventilation, suggesting its use for induction of anesthesia in cases where maintenance of spontaneous ventilation is desirable.